1. Field of the Invention
This invention relates to peptide sequences for the production of selective non-cross-reactive antipeptide antisera for the detection of human cyclooxygenase-1 and cyclooxygenase-2 proteins.
2. Brief Description of Disclosure in the Art
Non-steroidal, anti-inflammatory drugs exert many of their anti-inflammatory, analgesic, antipyretic activity through the inhibition of prostaglandin G/H synthase, also known as cyclooxygenase. Until recently, only one form of cyclooxygenase had been characterized, this corresponding to cyclooxygenase-1 (COX-1 ), a constitutive enzyme originally identified in bovine seminal vesicles and subsequently cloned from ovine, murine, and human sources. More recently the gene for an inducible form of cyclooxygenase (cyclooxygenase-2; COX-2), which is distinct from the cyclooxygenase-1, has been cloned, sequenced and characterized from chicken, murine, rat and human sources.
Cyclooxygenase-2 is rapidly and readily inducible by a number of agents including mitogens, endotoxin, hormones, cytokines and growth factors. Given that prostaglandins have both physiological and pathological roles, we have concluded that the constitutive enzyme, cyclooxygenase-1, is responsible for much of the endogenous basal release of prostaglandins and hence is important in their physiological functions which include the maintenance of gastrointestinal integrity and renal blood flow. In contrast the inducible form of the enzyme, cyclooxygenase-2, is mainly responsible for the pathological effects of prostaglandins where rapid induction of the enzyme would occur in response to inflammatory agents, hormones, growth factors, and cytokines. Currently, there are no reagents, such as specific polyclonal antisera or monoclonal antibodies, selective enough to permit the specific identification of the human COX-1 protein. To date, existing antisera developed have been cross-reactive, and react with both COX-1 and COX-2, thus rendering it difficult to distinguish between the two proteins. Mutually exclusive specific antibody reagents would greatly aid in the evaluation of the individual contributions of either COX-1 or COX-2 to pathological conditions.
Accordingly, it is an object of this invention to provide antibody reagents that permit the selective identification and quantification of cyclooxygenase-1 and cyclooxygenase-2 proteins in important biological preparations.